Asymmetric dimethylarginine induces maladaptive function of the blood-brain barrier.
| Autor: | Buzhdygan TP; Department of Neural Sciences, Alzheimer's Center at Temple, Temple University Lewis Katz School of Medicine, Philadelphia, PA, United States., Ramirez SH; Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL, United States., Nenov MN; Department of Psychology and Neuroscience, College of Liberal Arts, Temple University, Philadelphia, PA, United States. |
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| Jazyk: | angličtina |
| Zdroj: | Frontiers in cell and developmental biology [Front Cell Dev Biol] 2024 Oct 09; Vol. 12, pp. 1476386. Date of Electronic Publication: 2024 Oct 09 (Print Publication: 2024). |
| DOI: | 10.3389/fcell.2024.1476386 |
| Abstrakt: | Growing body of evidence suggests that cardiovascular risk factor, asymmetric dimethylarginine (ADMA), can be implicated in the pathogenesis of neurodegenerative and psychiatric disorders. In part, ADMA can affect brain health negatively modulating critical functions of the blood-brain barrier (BBB). The precise mechanisms and consequences of ADMA action on the cerebral vasculature remains unexplored. Here, we evaluated ADMA-induced maladaptation of BBB functions by analyzing real time electrical cell-substrate impedance, paracellular permeability, immune-endothelial interactions, and inflammatory cytokines production by primary human brain microvascular endothelial cells (hBMVEC) treated with ADMA. We found that ADMA disrupted physical barrier function as evident by significant decrease in electrical resistance and increase in paracellular permeability of hBMVEC monolayers. Next, ADMA triggered immune-endothelial interactions since adhesion of primary human monocytes and their extravasation across the endothelial monolayer both were significantly elevated upon treatment with ADMA. Increased levels of cell adhesion molecules (VCAM-1 and RANTES), VEGF-A and inflammatory cytokines (IL-1β, TNF-α, IL-6, IL-10, IL-4, IL-2, IL-13, IL-12p70) characterize ADMA-induced hBMVEC dysfunction as inflammatory. Overall, our data suggest that ADMA can impair BBB functions disrupting the endothelial barrier and eliciting neuroinflammatory and neuroimmune responses. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision. (Copyright © 2024 Buzhdygan, Ramirez and Nenov.) |
| Databáze: | MEDLINE |
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